1. Field of the Invention
This invention relates to a monoclonal antibody (hereinafter at times referred to as a MoAb) capable of distinguishing human hepato-carcinoma cells, a hybridoma producing said monoclonal antibody and a process for preparing the monoclonal antibody by using said hybridoma. It also relates to the application of said monoclonal antibody. In particular, this invention relates to a monoclonal antibody which is capable of specifically distinguishing human hepato-carcinoma cells from normal cells and of damaging only hepato-carcinoma cells in vivo.
2. Prior Art
It was reported by Koehler and Milstein in 1975 that a hybridoma was prepared between P3X63-Ag8 (HGPRT-deficient strain), which is a mutant strain of mouse myeloma P3K, and a cell strain which produces anti-sheep red blood cell antibody, and that the hybridoma has self-growing ability and anti-sheep red blood cell antibody producing ability, as well. The concept of a homogeneous antibody which is capable of distinguishing only a single antigenic determinant, that is, the concept of the monoclonal antibody introduced in this research has received considerable attention in the fields of immunology, iatrology, pharmacology and biology. In 1977, H. Koprowski et al, at the Wistar Institute, prepared hybridomas which produce MoAb against viruses or malignant tumors. They showed the availability and effectiveness of the MoAb as an agent and suggested its possibility as a pharmaceutical agent. Since said antibody might specifically distinguish tumor specific antigens, their report with particular respect to the preparation of an anti-malignant tumor antibody has received considerable attention in the clinical field of the treatment of tumors where accompanying normal cell damage had previously been a problem. That is to say, an antibody capable of specifically distinguishing tumor specific antigens can specifically distinguish tumor cells without reacting with normal cells, even if both of the cells have been generated from the same individual. It has been expected that a treatment aiming at tumor cells as the sole targets may be realized if the antibody is cytotoxic in itself or otherwise combined with an anti-tumor agent.
For the purpose of realizing this expectation, attempts have been carried out to prepare MoAbs against various tumor cells [Proc. Natl. Acad. Sci. 75, 3405 (1978); Proc. Natl. Acad. Sci. 76, 1438 (1079); Proc. Natl. Acad. Sci. 77, 6841 (1980); Br. J. Cancer 43, 696 (1981)]. However, it has been found that the MoAbs thus obtained did not always distinguish only tumor specific antigens because they showed cross reactivity with normal cells, and further, that even if some of the MoAbs were found to be tumor specific, they showed that effect only on some limited leukemia cells while showing no therapeutic effect on solid tumors, such as hepatoma and the like, when applied to the treatment of tumors in vivo [Cancer Res., 40, 3147 (1980); Blood, 58, 141 (1981)].
Accordingly, the necessary prerequisites for an antibody applicable to the treatment of tumors is, first of all, that the antibody be specific to tumor cells and have no reactivity with normal cells, and secondly, that it be actually cytotoxic to tumor cells in vivo. However, no MoAb has been reported which satisfies both of these requirements and is effective as an antitumor agent. Furthermore, the MoAb prepared by this invention, which is useful for the treatment of hepato-carcinoma cells, has not been reported at all.
Most of the current treatments of hepato-carcinoma rely on excision, but such treatment by excision has a limit. Although it is said that up to 70-80% of liver volume can be excised, in the case of cirrhosis, there are sometimes cases where the regeneration of liver after excision cannot be expected, and in such cases, cirrhosis will be promoted after excision. Also, in the therapy of hepato-carcinoma with a drug such as a chemotherapeutic agent or the like, various attempts have been made including modification of the occasion, interval, route and site of the administration, but no reliable method or case has been reported showing a satisfactory therapeutic effect. Therefore, it is earnestly desired to develop a MoAb which is capable of specifically distinguishing hepato-carcinoma cells and specifically attacking them.